Cell-nonautonomous control of the UPR: Mastering energy homeostasis

Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in hypothalamic neurons are common features of obesity, resulting in leptin and insulin resistance. In this issue, Williams et al. (2014) demonstrate, for the first time, cell-nonautonomous UPR signaling between brain and liver in the context of glucoregulation.